ArticleProceedings of the National Academy of Sciences of the United States of America1996
In vitro activation of the interferon-induced, double-stranded RNA-dependent protein kinase PKR by RNA from the 3' untranslated regions of human alpha-tropomyosin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 101 citations in OpenAlex.
- The Epitranscriptome in Translation Regulation.Cold Spring Harbor perspectives in biology · 2019Review
- The search for a PKR code-differential regulation of protein kinase R activity by diverse RNA and protein regulators.RNA (New York, N.Y.) · 2019Review
- Self-Amplifying RNA Vaccines Give Equivalent Protection against Influenza to mRNA Vaccines but at Much Lower Doses.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Interaction of PKR with single-stranded RNA.Scientific reports · 2017Article
- The Role of Gammaherpesviruses in Cancer Pathogenesis.Pathogens (Basel, Switzerland) · 2016Review
- Mechanistic Analysis of Activation of the Innate Immune Sensor PKR by Bacterial RNA.Journal of molecular biology · 2015Article
- Potential role for snoRNAs in PKR activation during metabolic stress.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Genome-wide analysis of Staufen-associated mRNAs identifies secondary structures that confer target specificity.Nucleic acids research · 2013Article
- Interferon-induced RIP1/RIP3-mediated necrosis requires PKR and is licensed by FADD and caspases.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Regulatory Roles for Long ncRNA and mRNA.Cancers · 2013Article
- Native tertiary structure and nucleoside modifications suppress tRNA's intrinsic ability to activate the innate immune sensor PKR.PloS one · 2013Article
- Regulation of innate immunity through RNA structure and the protein kinase PKR.Current opinion in structural biology · 2011Review
- Tumor suppression by RNA from C/EBPβ 3'UTR through the inhibition of protein kinase Cε activity.PloS one · 2011Article
- Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activation.Nucleic acids research · 2010Article
- Virus-based microRNA expression for gene functional analysis in plants.Plant physiology · 2010Article
- Article
- Intrinsic cellular defenses against virus infection by antiviral type I interferon.Yonsei medical journal · 2010Review
- Sequence-non-specific effects of RNA interference triggers and microRNA regulators.Nucleic acids research · 2010Review
- Article
- Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability.Molecular therapy : the journal of the American Society of Gene Therapy · 2008Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cellular kinase known as PKR (protein kinase RNA-activated) is induced by interferon and activated by RNA. PKR is known to have antiviral properties due to its role in translational control. Active PKR phosphorylates eukaryotic initiation factor 2 alpha and leads to inhibition of translation, including viral translation. PKR is also known to function as a tumor suppressor, presumably by limiting the rate of tumor-cell translation and growth. Recent research has shown that RNA from the 3' untranslated region (3'UTR) of human alpha-tropomyosin has tumor-suppressor properties in vivo [Rastinejad, F., Conboy, M. J., Rando, T. A. & Blau, H. M. (1993) Cell 75, 1107-1117]. Here we report that purified RNA from the 3'UTR of human alpha-tropomyosin can inhibit in vitro translation in a manner consistent with activation of PKR. Inhibition of translation by tropomyosin 3'UTR RNA was observed in a rabbit reticulocyte lysate system, which is known to contain endogenous PKR but was not seen in wheat germ lysate, which is not responsive to a known activator of PKR. A control RNA purified in the same manner as the 3'UTR RNA did not inhibit translation in either system. The inhibition of translation observed in reticulocyte lysates was prevented by the addition of adenovirus virus-associated RNA1 (VA RNAI), an inhibitor of PKR activation. Tropomyosin 3'UTR RNA was bound by immunoprecipitated PKR and activated the enzyme in an in vitro kinase assay. These data suggest that activation of PKR could be the mechanism by which tropomyosin 3'UTR RNA exerts its tumor-suppression activity in vivo.
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